The structure of the Na+,K+-ATPase and mapping of isoform differences and disease-related mutations.
The Na+,K+-ATPase transforms the energy of ATP to the maintenance of steep electrochemical gradients for sodium and potassium across the plasma membrane. This activity is tissue specific, in particular due to variations in the expressions of the alpha subunit isoforms one through four. Several mutations in alpha2 and 3 have been identified that link the specific function of the Na+,K+-ATPase to the pathophysiology of neurological diseases such as rapid-onset dystonia parkinsonism and familial hemiplegic migraine type 2. We show a mapping of the isoform differences and the disease-related mutations on the recently determined crystal structure of the pig renal Na+,K+-ATPase and a structural comparison to Ca2+-ATPase. Furthermore, we present new experimental data that address the role of a stretch of three conserved arginines near the C-terminus of the alpha subunit (Arg1003-Arg1005).
Morth
J Preben
JP
Centre for Membrane Pumps in Cells and Disease-PUMPKIN, Danish National Research Foundation, University of Aarhus, Gustav Wieds Vej 10C, Aarhus C, Denmark.
Poulsen
Hanne
H
Toustrup-Jensen
Mads S
MS
Schack
Vivien Rodacker
VR
Egebjerg
Jan
J
Andersen
Jens Peter
JP
Vilsen
Bente
B
Nissen
Poul
P
D000818:Animals; D019556:COS Cells; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D006801:Humans; D008881:Migraine Disorders / Q000235:genetics; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D012313:RNA / Q000235:genetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics* / Q000378:metabolism*; D013552:Swine
D020033:Protein Isoforms; D021122:Protein Subunits; D012313:RNA; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase